Pentose phosphate pathway

Pentose phosphate pathway also refers to “HMP- pathway” stands for Hexose Mono- Phosphate Pathway. It is very different from the other pathways, where it neither releases ATP nor consumes ATP during the process. Pentose phosphate pathway occurs in all types of cells and tissues. In the liver, 30% of glucose is metabolized by the Pentose phosphate pathway. The process of Pentose phosphate pathway occurs in the Cytoplasm.

It produces NADPH which in turn involves in the synthesis of fatty acids that involves about 50% of the NADPH molecules. In addition to this, the NADPH molecule also involves in the oxidative stress homeostasis and synthesis of cytochrome P450 enzymes. Pentose phosphate pathway also produces trioses, pentoses and hexoses where the production of pentoses helps in the nucleotide synthesis.

Content: Pentose phosphate pathway

  1. History
  2. Meaning of Pentose phosphate pathway
  3. Phases of Pentose phosphate pathway
  4. Process of Pentose phosphate pathway
  5. Occurrence
  6. Significance

History

YearScientistDiscoveryWon Nobel prize
1930sOtto WarburgDiscovered NADP during the oxidation of glucose 6-phosphate to 6-phosphogluconate1931 in physiology or medicine
1950sEfraim Racker and Fritz LipmannDiscovered the co-enzyme-A1953 in physiology or medicine

Meaning of Pentose phosphate pathway

Pentose phosphate pathway can define as a metabolic pathway that occurs in all living organisms which utilize the first intermediate product of glycolysis i.e. Glucose 6-phosphate for the production of NADPH (by the reduction of coenzyme NADP) and a Pentose sugar.

Phases of Pentose phosphate pathway

In the Pentose phosphate pathway, there are two phases namely “Oxidative” and “Non-oxidative”.

Oxidative phase: There is an oxidation i.e. loss of electrons during this phase. It involves the oxidation of Glucose 6-phosphate (6-C phosphorylated sugar) into Ribulose 5-phosphate (5-C phosphorylated sugar).

Non-oxidative phase: This phase does not involve the oxidation process. In this phase, Ribulose 5-phosphate acts as an intermediate which produces several phosphorylated carbohydrates which then participates in the synthesis of nucleotides, fatty acid etc.

Process of Pentose phosphate pathway

The process of Pentose phosphate pathway can be summarized into two phases i.e. oxidative and non-oxidative phase.

Steps of the oxidative phase

First, 6 molecules of Glucose 6-phosphate oxidizes into 6-phosphoglucolactone in the presence of 6 coenzyme NADP molecules. The conversion is catalyzed by the enzyme “Glucose 6-phosphate dehydrogenase”. This first step of PPP (Pentose phosphate pathway) releases 6 molecules of NADPH2.

ppp step 1

Then, 6 molecules of 6-phosphoglucolactone hydrolyze into 6-phosphogluconic acid by the water. “Lactonase” is the enzyme which carries out this conversion.

ppp step 2
6 molecules of 6-phosphogluconic acid undergo oxidative carboxylation into Ribulose 5-phosphate in the presence of 6 coenzyme NADP molecules. The conversion is catalyzed by the enzyme “Phosphogluconic acid dehydrogenase”. This step releases 6 molecules of NADPH2.

ppp step 3

Steps of the non-oxidative phase

6 molecules of Ribulose 5-phosphate undergo isomerization by an enzyme “Ribulose phosphate 3-epimerase” and “Pentose phosphate isomerase” into 4 molecules of Xylulose 5-phosphate and 2 molecules of Ribose 5-phosphate respectively.

ppp step 4
Then 2 molecules of Xylulose 5-phosphate and 2molecules of Ribose 5-phosphate combine to form 2 molecules of sedoheptulose 7-phosphate and two molecules of 3-phosphoglyceraldehyde. This reaction is catalyzed by “Transketolase”.

ppp step 5
2 molecules of sedoheptulose 7-phosphate and 2 molecules of 3- phosphoglyceraldehyde combine to form 2 molecules of Fructose 6-phosphate and 2 molecules of erythrose 4-phosphate. This reaction is catalyzed by “Transaldolase”.

ppp step 6
1 molecule of 3- phosphoglyceraldehyde isomerizes into Dihydroxyacetone-phosphate by an enzyme “Phosphotriose isomerase”.

ppp
1 molecule of 3- phosphoglyceraldehyde combines with the Dihydroxyacetone-phosphate and converts into Fructose 1, 6-biphosphate by an enzyme “Aldolase”. Fructose 1, 6-biphosphate later converts into Fructose 6-phosphate by an enzyme “Phosphatase”.

ppp step 8
Therefore, 5 molecules of Fructose 6-phosphate converts into glucose 6-phosphate. “Phosphohexose isomerase” is an enzyme that catalyzes this reaction.

ppp step 9

Net production: The net production of Pentose phosphate pathway includes 6 molecules of CO2 and 6 molecules of NADPH2.

Occurrence

Pentose phosphate pathway occurs in all living organisms but at different sites for example:

In animal cell: PPP occurs in the cytosol or cytoplasm of the cell.
Plant cell: PPP occurs in the plastid.
In humans: It varies from tissues to tissues.

Significance

Pentose phosphate pathway is an alternative pathway for the carbohydrate degradation or breakdown as it directly oxidizes the glucose 6-phosphate without entering into the glycolysis cycle.

Ribulose 5-phosphate being a primary acceptor of CO2, it involves in the CO2 fixation of the photosynthetic organisms during the Calvin-cycle. Ribulose 5-phosphate also helps in the synthesis of Riboflavin.

Another intermediate of PPP is Ribose 5-phosphate which helps in the nucleotide and nucleic acid synthesis. Erythrose 4-phosphate helps in the synthesis of phenylalanine, tryptophan, tyrosine etc.

Sedoheptulose 7-phosphate helps in the synthesis of heptoses in the lipopolysaccharide layer of gram-negative bacteria. The NADPH2 produced in the Pentose phosphate pathway helps in the reduction biosynthesis of fatty acids, steroid hormones etc.

Pentose phosphate pathway also plays an essential role in the RBCs to produce NADPH2, as they lack mitochondria. It is the only cytoplasmic pathway that generates only NADPH2 as the energy source but not ATP.

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